U. expert ties cells to strokes

The very blood cells that promote clotting, fight infection and reduce inflammation also start a series of molecular events that lead to heart attack, stroke, clogged arteries and other inflammatory diseases, according to research from the University of Utah and the University of South Carolina.

It's a matter of communication between key human blood cells, monocytes and platelets, according to Dr. Guy Zimmerman, U. School of Medicine professor of internal medicine and senior author of the study, published online in the Journal of Clinical Investigation. Zimmerman and a former member of his team, Dan A. Dixon, now at University of South Carolina, led the research.

By understanding the details of how the two affect production of Cox-2, the researchers believe they may learn how it occurs in the wrong place, at the wrong time or in the wrong amount and becomes uncontrolled. "We've identified several different checkpoints for genetic information to be translated into protein," he says.

"Ultimately, one of the things we hope for is a way to intervene, with therapeutic drugs, to turn this off when it's occurring in an injurious fashion" — in heart attack and stroke, for example. The scientists believe they can also learn from this research how other genes might be controlled, as well.

The researchers figured out how two key human blood cells, platelets and monocytes, talk to each other. The process can cause healing, but when the "conversation" triggers the wrong production level of the enzyme Cox-2, it can lead to disease.

Platelets are best known for their role in clotting and thrombosis, he says, while monocytes are white blood cells involved in inflammation control. "These cells have unique roles in clotting, wound healing and defense against infection. It is the irony and the paradox that each also plays major roles in human diseases," Zimmerman says.

The researchers are trying to understand the entire process by which cells so central to the defense of the body and the well-being of healthy humans "can go bad."

It can happen if one of the cell types turns on a gene inappropriately, creating "too much or at the wrong time in the wrong place."

For this study, they looked at the gene that codes for Cox-2. Many people are familiar with Cox-2 because of popular Cox-2 inhibitors, such as Vioxx. While that medication effectively reduced inflammation in diseases such as arthritis, it had the unintended consequence of increasing the risk of heart attack.

Platelets and monocytes play individual roles in a body's function, but they also pass molecular information between them.